Early versus Later Anticoagulation for Stroke with Atrial Fibrillation

The study described in the given abstract aimed to determine whether early initiation of direct oral anticoagulants (DOACs) would be more effective than later initiation in individuals with atrial fibrillation who had experienced an acute ischemic stroke. The trial was conducted at 103 sites in 15 countries and involved randomizing participants to receive either early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). The primary outcome assessed was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the individual components of the primary outcome at 30 and 90 days.

A total of 2013 participants were included in the study, with 37% having a minor stroke, 40% having a moderate stroke, and 23% having a major stroke. Of these, 1006 were assigned to early anticoagulation, while 1007 were assigned to later anticoagulation. The primary outcome occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group by 30 days. The risk difference between the two groups was -1.18 percentage points, with a 95% confidence interval (CI) ranging from -2.84 to 0.47. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group by 30 days, and in 18 participants (1.9%) and 30 participants (3.1%) by 90 days. The odds ratio for recurrent ischemic stroke at 30 days was 0.57 (95% CI, 0.29 to 1.07), and at 90 days it was 0.60 (95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.

Based on the findings of this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to be 2.8 percentage points lower to 0.5 percentage points higher with early use of DOACs compared to later use, within the range of the 95% confidence interval.

In conclusion, this study investigated the timing of DOAC initiation in individuals with atrial fibrillation following an acute ischemic stroke. The results suggest that there was no significant difference in the occurrence of the primary composite outcome between early and later initiation of DOACs. Furthermore, the incidence of recurrent ischemic stroke and symptomatic intracranial hemorrhage did not significantly differ between the two groups. These findings contribute to the understanding of optimal anticoagulation strategies in this patient population and provide important insights for clinical decision-making.

 

DOI: 10.1056/NEJMoa2303048


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